scholarly journals Multidrug Resistance Protein 2-Mediated Estradiol-17β-d-glucuronide Transport Potentiation: In Vitro-in Vivo Correlation and Species Specificity

2008 ◽  
Vol 37 (4) ◽  
pp. 794-801 ◽  
Author(s):  
K. Herédi-Szabó ◽  
H. Glavinas ◽  
E. Kis ◽  
D. Méhn ◽  
G. Báthori ◽  
...  
2016 ◽  
Vol 76 ◽  
pp. 11-17 ◽  
Author(s):  
Flavia Temperilli ◽  
Manuela Di Franco ◽  
Isabella Massimi ◽  
Maria Luisa Guarino ◽  
Maria Paola Guzzo ◽  
...  

2014 ◽  
Vol 737 ◽  
pp. 159-167 ◽  
Author(s):  
Li-Ming Lien ◽  
Zhih-Cherng Chen ◽  
Chi-Li Chung ◽  
Ting-Lin Yen ◽  
Hou-Chang Chiu ◽  
...  

2014 ◽  
Vol 58 (12) ◽  
pp. 7390-7397 ◽  
Author(s):  
Maria Isabel Veiga ◽  
Nuno S. Osório ◽  
Pedro Eduardo Ferreira ◽  
Oscar Franzén ◽  
Sabina Dahlstrom ◽  
...  

ABSTRACTPlasmodium falciparumhas the capacity to escape the actions of essentially all antimalarial drugs. ATP-binding cassette (ABC) transporter proteins are known to cause multidrug resistance in a large range of organisms, including theApicomplexaparasites.P. falciparumgenome analysis has revealed two genes coding for the multidrug resistance protein (MRP) type of ABC transporters:Pfmrp1, previously associated with decreased parasite drug susceptibility, and the poorly studiedPfmrp2. The role ofPfmrp2polymorphisms in modulating sensitivity to antimalarial drugs has not been established. We herein report a comprehensive account of thePfmrp2genetic variability in 46 isolates from Thailand. A notably high frequency of 2.8 single nucleotide polymorphisms (SNPs)/kb was identified for this gene, including some novel SNPs. Additionally, we found thatPfmrp2harbors a significant number of microindels, some previously not reported. We also investigated the potential association of the identifiedPfmrp2polymorphisms with alteredin vitrosusceptibility to several antimalarials used in artemisinin-based combination therapy and with parasite clearance time. Association analysis suggestedPfmrp2polymorphisms modulate the parasite'sin vitroresponse to quinoline antimalarials, including chloroquine, piperaquine, and mefloquine, and association within vivoparasite clearance. In conclusion, our study reveals that thePfmrp2gene is the most diverse ABC transporter known inP. falciparumwith a potential role in antimalarial drug resistance.


2006 ◽  
Vol 80 (24) ◽  
pp. 12236-12247 ◽  
Author(s):  
Iñigo Narvaiza ◽  
Oscar Aparicio ◽  
María Vera ◽  
Nerea Razquin ◽  
Sergia Bortolanza ◽  
...  

ABSTRACT RNA interference with viral vectors that express short hairpin RNAs (shRNAs) has emerged as a powerful tool for functional genomics and therapeutic purposes. However, little is known about shRNA in vivo processing, accumulation, functional kinetics, and side effects related to shRNA saturation of the cellular gene silencing machinery. Therefore, we constructed first-generation recombinant adenoviruses encoding different shRNAs against murine ATP-binding cassette multidrug resistance protein 2 (Abcc2), which is involved in liver transport of bilirubin to bile, and analyzed Abcc2 silencing kinetics. C57/BL6 mice injected with these viruses showed significant impairment of Abcc2 function for up to 3 weeks, as reflected by increased serum bilirubin levels. The lack of Abcc2 function correlated with a specific reduction of Abcc2 mRNA and with high levels of processed shRNAs targeting Abcc2. Inhibition was lost at longer times postinfection, correlating with a decrease in the accumulation of processed shRNAs. This finding suggests that a minimal amount of processed shRNAs is required for efficient silencing in vivo. This system was also used to evaluate the effect of shRNA expression on the saturation of silencing factors. Saturation of the cellular silencing processing machinery alters the accumulation and functionality of endogenous microRNAs (miRNAs) and pre-miRNAs. However, expression of functional exogenous shRNAs did not change the levels of endogenous miRNAs or their precursors. In summary, this work shows that adenoviral vectors can deliver sufficient shRNAs to mediate inhibition of gene expression without saturating the silencing machinery.


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